Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt

Psychopharmacology (Berl). 2008 Apr;197(3):371-7. doi: 10.1007/s00213-007-1041-3. Epub 2007 Dec 15.


Aims: To examine the effect of varenicline, a selective alpha4-beta2 nicotinic acetylcholine receptor (nAChR) partial agonist, on craving and withdrawal symptoms in smokers making a quit attempt and the rewarding effects of smoking during a lapse after the target quit date (TQD).

Materials and methods: Pooled data were analysed from two identical double-blind, randomised trials comparing varenicline 1 mg BID, bupropion (sustained release) 150 mg BID and placebo using measures of craving and withdrawal in the first week after the TQD (in abstinent [n = 612] and non-abstinent participants [n = 1,155]) and of the rewarding effects of the first cigarette smoked in non-abstinent participants.

Results: In abstinent and non-abstinent participants combined, varenicline reduced craving more than bupropion (p < 0.01) and placebo (p < .001); the effect did not differ by whether or not subjects were abstinent; bupropion reduced craving more than placebo (p < 0.001). Among abstinent participants, both varenicline and bupropion reduced negative affect more than those receiving placebo (p < 0.005). Neither active drug reduced restlessness, insomnia or appetite vs placebo. Varenicline reduced ratings of satisfaction and psychological reward after the first cigarette smoked after the TQD vs bupropion (p < 0.005) and placebo (p < 0.001); bupropion also reduced these more than placebo (p < 0.05).

Conclusions: Varenicline significantly reduces craving and the rewarding effects of smoking after the TQD to a greater extent than bupropion, which may contribute to varenicline's greater efficacy for smoking cessation. Varenicline's lack of effect in reducing insomnia, restlessness and increased appetite in this analysis suggests that receptors other than the alpha4-beta2 nAChR subtype may be implicated in these withdrawal symptoms.

Trial registration: ClinicalTrials.gov NCT00141206 NCT00143364.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Aged
  • Benzazepines / therapeutic use*
  • Bupropion / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Delayed-Action Preparations
  • Dopamine Uptake Inhibitors / therapeutic use*
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Motivation*
  • Multicenter Studies as Topic
  • Nicotine / adverse effects*
  • Nicotinic Agonists / pharmacology*
  • Quinoxalines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Smoking Cessation*
  • Substance Withdrawal Syndrome / drug therapy*
  • Tobacco Use Disorder / rehabilitation*
  • Varenicline


  • Benzazepines
  • Delayed-Action Preparations
  • Dopamine Uptake Inhibitors
  • Nicotinic Agonists
  • Quinoxalines
  • Bupropion
  • Nicotine
  • Varenicline

Associated data

  • ClinicalTrials.gov/NCT00141206
  • ClinicalTrials.gov/NCT00143364